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TG-interacting factor 1 acts as a transcriptional repressor of sterol O-acyltransferase 2
Camilla Pramfalk1, Tiffany A Melhuish, David Wotton
1Division of Clinical Chemistry, Department of Laboratory Medicine, and Centre for Nutrition and Toxicology, NOVUM, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Abstract:
Acat2 [gene name: sterol O-acyltransferase 2 (SOAT2)] esterifies cholesterol in enterocytes and hepatocytes. This study aims to identify repressor elements in the human SOAT2 promoter and evaluate their in vivo relevance. We identified TG-interacting factor 1 (Tgif1) to function as an important repressor of SOAT2. Tgif1 could also block the induction of the SOAT2 promoter activity by hepatocyte nuclear factor 1α and 4α. Women have ∼ 30% higher hepatic TGIF1 mRNA compared with men. Depletion of Tgif1 in mice increased the hepatic Soat2 expression and resulted in higher hepatic lipid accumulation and plasma cholesterol levels. Tgif1 is a new player in human cholesterol metabolism.
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